Ki67 and breast cancer mortality in women with invasive breast cancer.
Probert J., Dodwell D., Broggio J., Charman J., Dowsett M., Kerr A., McGale P., Taylor C., Darby SC., Mannu G.
BACKGROUND: The percentage of cells staining positive for Ki67 is sometimes used for decision-making in early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut-points and the influence of inter-laboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for inter-laboratory variability and eight patient and tumor characteristics. METHODS: A multicentre cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until 31st December 2020. RESULTS: Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, HER2-negative early IBC (ptrend<0.001). This relationship remained strong after adjustment for patient and tumor characteristics (ptrend <0.001). Standardization for inter-laboratory variability did little to alter these results. For women with Ki67 scores of 0 to 5%, 6-10%, 11-19% and 20-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (2.8-4.0), 3.7% (3.0 to 4.4), 3.4% (2.8-4.1), and 3.4% (2.8-4.1), whereas for women with Ki67 scores 30-39% and 40-100%, these risks were higher, at 5.1% (4.3 to 6.2) and 7.7% (6.6 to 9.1) (ptrend<0.001). Similar results were obtained when the adjusted analysis was repeated omitting pathological information about tumor size and nodal involvement, which would not be available pre-operatively for patients being considered for neoadjuvant therapy. CONCLUSION: Our findings confirm the prognostic value of Ki67 scores ≥30% in women with ER-positive, HER2-negative early IBC, irrespective of inter-laboratory variability. They also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.